e., HIV patients), however probably at lower rate compared to HPD. The characterizations of HPD and PsPD mechanisms and the identification of common definition criteria are the next future challenges in this area of cancer research.Immune checkpoint inhibitors (ICI) have been validated as an effective new treatment strategy in several tumoral types including lung cancer. This remarkable shift in the therapeutic paradigm is in large part due to the duration of responses and long-term survival seen with ICI. However, despite this, the majority of cancer patients do not experience benefit from ICI. Even among patients who initially respond to ICI, disease progression may ultimately occur. Moreover, in some patients, these drugs may be associated with new patterns of progression such as pseudo-progression and hyper-progressive disease, and different toxicity profiles with immune-related adverse events. Therefore, the identification of predictive biomarkers may help to select those patients most likely to obtain a true benefit from these drugs, and avoid exposure to potential toxicity in patients who will not obtain clinical benefit, while also reducing the economic impact. In this review, we summarize current and promising potential predictive biomarkers of ICI in patients with non-small cell lung cancer (NSCLC), as well as pitfalls encountered with their use and areas of focus to optimize their routine clinical implementation.Immune checkpoint inhibitors (ICIs) have become the standard of care for the first-line treatment of advanced non-small cell lung cancer patients (NSCLC), either as single agents or combined with chemotherapy. The evidence sustaining their role for poor performance status (ECOG PS ?2) patients is limited.
We search PubMed and the proceedings of international oncology meetings to perform a systematic review to assess the outcomes poor PS NSCLC patients who received ICIs as first-line treatment. A meta-analysis included retrospective studies focusing on pembrolizumab monotherapy in PD-L1 ?50% NSCLC. We reported the global objective response rate (ORR), disease control rate (DCR) and landmark progression-free and overall survival (PFS and OS, respectively) in ECOG PS ?2 and 0-1 patients, respectively.
Forty-one studies were included in the systematic review. Thirty-two retrospective studies focused on pembrolizumab monotherapy in PD-L1 ?50% cases. In total, 1,030 out of 5,357 (19%) of patients across 30 ste factors conditioning it, and the development of dedicated treatment strategies is required to improve the outcomes in this patient population.
Still with limited prospective evidence sustaining the role of immunotherapy in previously untreated NSCLC with poor PS, 19% of patients in retrospective series dealing with pembrolizumab in PD-L1 ?50% tumors had an ECOG PS ?2. https://www.selleckchem.com/products/bda-366.html Clinical effort encompassing the definition of poor PS, of the factors conditioning it, and the development of dedicated treatment strategies is required to improve the outcomes in this patient population.Treatment of oncogene-addicted non-small cell lung cancer (NSCLC) has been changed by the advent of tyrosine kinase inhibitors (TKIs). Albeit great benefits are achieved with target therapies, resistance invariably occurs and recourse to alternative treatments is unavoidable. Immune checkpoint inhibitors (ICIs) role and the best setting of immunotherapy administration in oncogene-driven NSCLC are matter of debate.
We performed a systematic literature review through PubMed, in order to gather all the available information regarding ICI activity and efficacy in oncogene-addicted NSCLC, from both prospective trials and retrospective series. A meta-analysis of objective response rate in different molecular subgroups was provided. Combinatorial strategies including ICIs and related toxicities were also recorded.
Eighty-seven studies were included in the qualitative analysis. mutation may be a biomarker of poor response to single-agent ICIs (7% of -mutant NSCLC patients achieved disease response in prospKIs and ICIs in early-stage disease, molecular characterization will become fundamental in this setting.
In oncogene-addicted NSCLC (with the exception of KRAS-mutated), ICIs are usually administered at the failure of other treatment options, but administering single-agent immunotherapy in later disease phases may limit its efficacy. With the progressive administration of TKIs and ICIs in early-stage disease, molecular characterization will become fundamental in this setting.The advent of immune-checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis, both as monotherapy and in combination strategies, produced a paradigm change of the treatment algorithm for metastatic, non-oncogene addicted, non-small cell lung cancer (NSCLC) patients. Although the great efficacy and the optimal tolerability emerging from clinical studies has been confirmed for the majority of patients treated in the real-word scenario, however the potential activity and safety profile of these agents in uncommon NSCLC populations remains still controversial. Particularly, patients with previously diagnosed autoimmune disease or concomitant steroids treatment at the time of immunotherapy initiation represent two special subgroups of patients not unusual in the real-word practice, to whom the clinical implication of immune-checkpoint inhibitors administration is largely unknown. In this review we provided an updated literature overview, summarizing available evidence and reporting practical suggestions, which may guide physicians in their clinical management of these NSCLC sub-populations.Although brain metastases occur in almost one-third of non-small cell lung cancer (NSCLC) patients, and immune checkpoint inhibitors (ICI) either as monotherapy or combined with chemotherapy are the new standard of care in the first line setting, most trials excluded patients with asymptomatic and/or untreated brain metastases. Brain metastases have a major clinical impact due to the worsening of the patient's prognosis and quality of life. Furthermore, the incidence of brain metastases is increasing in NSCLC patients, due to a longer survival and better imaging techniques. Therefore, brain metastases are increasingly becoming a research topic. Recent clinical data endorses ICI as a therapeutic strategy in this subpopulation of NSCLC patients, although the immune environment in brain metastases is more immune ignorant compared with the microenvironment in the primary tumour or in the extracranial metastases. In this review we summarize the current evidence of ICI strategy in NSCLC patients with brain metastases, including trial and real-life data.